Methacrylated Cartilage ECM-Based Hydrogels as Injectables and Bioinks for Cartilage Tissue Engineering

Abstract

Articular cartilage (AC) possesses a limited healing potential, meaning that untreated focal joint defects typically progress, leading to the development of degenerative diseases such as osteoarthritis. Several clinical strategies exist that aim to regenerate AC; however, recapitulation of a fully functional, load-bearing tissue remains a significant challenge. This can be attributed, at least in part, to a paucity of biomaterials that truly mimic the native tissue and provide appropriate cues to direct its regeneration. The main structural component of articular cartilage, type II collagen, does not readily gelate at body temperature, challenging the development of cartilage extracellular matrix (cECM)-derived injectable hydrogels and bioinks for AC tissue engineering and bioprinting applications. Here, we describe the development and rheological characterisation of a methacrylated cartilage ECM-based hydrogel/bioink (cECM-MA), which could be photocrosslinked when exposed to ultraviolet (UV) light. Functionalisation of the collagen backbone with methacryloyl groups had a negligible effect on triple helix stability, as demonstrated by circular dichroism spectroscopy. These cECM-MA bioinks demonstrated shear-thinning properties and could be loaded with bone marrow mesenchymal stem cells (BM-MSCs), micro-extruded to generate self-supporting 3D constructs of predefined size and shape, and then photocrosslinked using UV light. Analysis of the cell-laden constructs showed that the BM-MSCs were viable post-printing and underwent chondrogenesis in vitro, generating a tissue rich in sulphated glycosaminoglycans and collagens. These results support the use of methacrylated, tissue-specific ECM-derived hydrogels as bioinks for 3D bioprinting and/or as injectables for cartilage tissue engineering applications.

Keywords

• bioinks
• cartilage
• bioprinting